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September 26, 2019

Bioartificial liver: Bridge to liver regeneration

By Jennifer Schutz

The liver has the
greatest regenerative capacity of any organ in the body. However, when the
liver is injured beyond its ability to regenerate itself, and a transplant is
not readily available, there are few options for patients.

Scott Nyberg, M.D., Ph.D.

Led by Scott Nyberg, M.D., Ph.D., researchers are refining their own version of a bioartificial liver, known as the Spheroid Reservoir Bioartificial Liver (SRBAL). This device contains pig liver cell (hepatocyte) spheroids, which replace a patient's liver function.

“Ideally, the
artificial liver would bridge the gap until a donor liver becomes available or
if it could help the patient avoid the need for a transplant altogether,” says
Dr. Nyberg.

While the artificial
liver device has been successfully
demonstrated on pigs with acute liver failure, the ultimate
goal is the bedside treatment of patients in liver failure. With aresearch grant from
Regenerative Medicine Minnesota, Dr. Nyberg and his team are continuing to
study whether the artificial liver could function similar to a kidney dialysis
machine. The patient would be connected to the device, and much like dialysis,
the artificial organ would, perform critical bodily functions while the liver
heals and regenerates.

“The results of our
third large animal study were published in January 2019,”
says Dr. Nyberg. “Pigs were chosen for the early studies because their
metabolism is similar to ours and because they could provide an abundant supply
of liver cells.”

In the treatment
group, all of the animals survived the therapy and were up walking around with
recovered livers at the end of the study. The results have paved the way for
future clinical trials.

Schematic of the extracorporeal circuit of the Spheroid Reservoir Bioartificial Liver

Although the SRBAL is
similar to kidney dialysis, the liver is more complicated. It does metabolic
activities, detoxifies wastes, and synthesizes proteins. Because of this, the
SRBAL incorporates living cells– in this case, from pig livers - to carry out
such vital functions for a patient.

“We’re ready for to
move into Phase I trials in humans,” says Dr. Nyberg. “However, funding a
medical device trial using living cells in humans is quite expensive, and we’ll
need to build a new clinically acceptable SRBAL suitable for human use.”

Once funding is
established and the new device developed, the first study in humans would be a
Phase I safety study to make sure the machine is safe for use on people. Second
is a dosing study to determine the efficient dose of liver cells to put in the
bioreactor to repair the liver. Once the Phase I and Phase II studies are complete
and encouraging, a Phase III, multicenter randomized study would follow.

“This is an exciting
time for transplant surgery,” says Charles Rosen,
M.D., director of the William J. von Liebig Center for
Transplantation and Clinic Regeneration at Mayo Clinic. “The need for organ
donation is high, and this research couldn’t come at a better time.”

SRBAL would be most
appropriate for patients who have acute liver failure and are awaiting
transplant, experience an overdose of medication, or those who aren’t
candidates for liver transplant.

“There’s a lot of work to be done, but this is a promising solution to the donor organ shortage in some cases” says Dr. Nyberg. “Many acute liver failure patients would have the opportunity to recover, if only they had time for their liver to regenerate and heal.”